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该研究或可打开未来生物疗法大门 资料来源：纽约大学朗格尼医学中心 / 纽约大学医学院 概要：科学家称，当细胞死亡时，某一种酶不能降解释放到血液中的DNA，这可能是狼疮炎症的一个主要诱因。 当细胞死亡时，某一种酶不能降解释放到血液中的DNA，这可能是狼疮炎症的一个主要诱因。纽约大学朗格尼医学中心研究人员在小鼠和人类患者身上进行的这一研究发现于6月9日在线发表在《细胞》杂志上。 该研究围绕哺乳动物细胞的持续健康周转展开。这些细胞会死亡，降解，组分（包括DNA）得到回收利用。研究人员发现，正常情况下，酶DNASE1L3会消化从细胞分裂中释放出来的小颗粒中的DNA，从而起到预防狼疮的作用。 如果没有DNASE1L3阻止其累积，那么积累起来的DNA就会诱发免疫细胞产生蛋白质抗体，这些抗体会摄取并移除这种DNA。这种抗体与DNA结合形成复合物后，进入动脉壁和人体组织，引起炎症，最严重的是系统性红斑狼疮（SLE），损害血管、皮肤、关节和肾脏。 研究报告的通讯作者、纽约大学朗格尼医学中心的病理学和医学教授鲍里斯·雷吉斯博士说，“我们的研究揭示出一种新机制，或可利用它来开发生物疗法，治疗狼疮和其他自身免疫疾病，这些疾病都是由于免疫系统错误地攻击自身细胞造成的。” 具体而言，研究人员培育出缺乏DNASE1L3基因的小鼠，在小鼠身上重建狼疮的疾病过程，包括DNA抗体形成和肾脏炎症产生。 雷吉斯说，“我们还证实了，缺乏DNASE1L3基因或者DNASE1L3基因紊乱的人类患者体内存在大量的循环DNA，且产生了针对它的抗体，这种抗体在大多数形式的狼疮中都存在。这项研究开辟了一个新的潜在治疗途径，包括可能将DNASE1L3作为药物施用。” 雷吉斯补充说，找到新疗法已经迫在眉睫，因为50年来，狼疮治疗领域鲜有进展，而传统上使用的药物耐受性较差。 报道来源： 上述报道转载自纽约大学朗格尼医学中心 / 纽约大学医学院提供的资料。注：资料可视内容和长度所需进行编辑。 以下为原文报道： ------------------ Enzyme keeps antibodies from targeting DNA, driving inflammation in lupus Study may open door to future biologic therapies Source: NYU Langone Medical Center / New York University School of Medicine Summary: Failure of an enzyme to break down DNA spilling into the bloodstream as cells die may be a major driver of inflammation in lupus, report scientists. Failure of an enzyme to break down DNA spilling into the bloodstream as cells die may be a major driver of inflammation in lupus. This is the finding of a study in both mice and human patients led by researchers at NYU Langone Medical Center and published online June 9 in the journalCell. The study revolves around the constant, healthy turnover of mammalian cells, which die, break up and have their parts, including DNA, recycled. Researchers found that an enzyme, DNASE1L3, normally digests the DNA within small particles issuing from disintegrating cells, thereby preventing lupus. Without DNASE1L3 to prevent its buildup, accumulating DNA triggers immune cells to produce proteins called antibodies that glom onto and remove the DNA. Such antibodies, when attached to DNA in complexes, get lodged in the walls of arteries and in tissues to cause inflammation that damages blood vessels, skin, joints and the kidneys as part of the most severe type of lupus, systemic lupus erythematosus (SLE). 'Our study reveals a new mechanism that could be harnessed for biological therapies for lupus and other autoimmune diseases, where the immune system mistakenly targets the body's own cells,' says senior study author Boris Reizis, PhD, professor of Pathology and Medicine at NYU Langone. Specifically, the study authors were able re-create lupus disease processes, including the formation of antibodies to DNA and kidney inflammation, by engineering mice that lacked the gene for DNASE1L3. 'We also confirmed that human patients with a missing or malfunctioning DNASE1L3 gene had an abundance of circulating DNA and developed antibodies to it, and that such antibodies were also present in most forms of lupus,' says Reizis. 'This opens up a potential avenue for a new treatment, including the possibility of administering DNASE1L3 as a drug.' The need to find new treatments is urgent, adds Reizis, because there have been few advances in the treatment of lupus in 50 years, and the drugs used traditionally are poorly tolerated.
Story Source: The above post is reprinted from materials provided by NYU Langone Medical Center / New York University School of Medicine. Note: Materials may be edited for content and length.
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